Glycerol-Modified Hydrogel for Wearable Iontophoresis-Driven Drug Delivery

Wearable epidermal devices are emerging as powerful tools for continuous, non-invasive health monitoring via sweat biomarker analysis. To enable on-demand sweat extraction when physiological sweat is absent, these systems must deliver specific drugs transdermally to stimulate secretion. Iontophoresis, which uses a mild electric current to transport charged drugs through the skin, is a promising solution. However, integrating drug reservoirs into wearable systems remains a challenge. Conventional hydrogels, used for drug delivery, suffer from fabrication complexity and rapid water loss, limiting shelf-life. This thesis addresses some of these issues by using agarose-based hydrogel modified with glycerol for improved long-term water retention. A scalable fabrication method was developed to integrate the agarose/glycerol hydrogel into a wearable iontophoretic device for sweat stimulation and collection. Inspired by stencil printing, the process uses an adhesive masking layer to define the deposition area and enables precise, blade-assisted application. A water-loss testing protocol was implemented to evaluate hydrogel shelf-life based on weight tracking and thickness monitoring via confocal laser scanning microscopy to quantify dehydration over time. A 60% glycerol concentration emerged as the optimal trade-off between water retention and electrical impedance. Refrigerated storage further reduced dehydration over 30 days due to lower evaporation in humid, cool conditions. Moreover, comparison with a commercial iontophoretic gel showed that the 60% glycerol hydrogel developed in this work had better water retention already after 5 days, the commercial gel lost about 28% of its weight, while the gel optimized in this work lost 23%. Furthermore after 30 days, the commercial gel was almost completely dry (about 95% weight loss), whereas the glycerol-based hydrogel kept its shape and even gained weight (about 3.6% weight loss) due to hygroscopic properties of glycerol, which help maintain hydration in the long term. A reproducible in vitro platform using a Strat-M membrane and agarose-gel phantom to simulate skin layers was introduced to support preclinical iontophoretic drug permeation. The in vitro platform was integrated into a custom optical setup to monitor iontophoretic permeation of a model dye, Neutral Red, within a skin-mimicking phantom. Neutral Red has a molecular weight and electrical charge at physiological pH that make it a suitable candidate for modeling pilocarpine, the drug commonly delivered transdermally for sweat stimulation in medical practice. Dye diffusion during stimulation was tracked in bright field using image sequences processed with a custom script for image analysis. Four experimental conditions were tested, no current, and current densities of 0.1, 0.3, and 0.5 mA/cm². The platform was successful in revealing the effects of current intensity on dye transport, showing an increase in dye penetration with higher current densities. This work presents a novel agarose/glycerol hydrogel formulation enhancing water retention toward long-term wearable iontophoretic devices. Furthermore, it introduces a scalable hydrogel loading method and a synthetic in vitro platform for iontophoresis performances tests. These advances support the development of more durable and effective systems for non-invasive wearable systems.